Receptor tyrosine kinases (RTKs) are transmembrane signaling proteins that transmit biological signals from the extracellular environment to the interior of the cell. The regulation of RTK signals is important for regulation of cell growth, differentiation, axonal growth, epithelial growth, development, adhesion, migration, and apoptosis (Prenzel et al. (2001) Endocr. Relat. Cancer 8:11-31; Hubbard and Till (2000) Annu. Rev. Biochem. 69:373-98). RTKs are known to be involved in the development and progression of several forms of cancer. In most of the RTK-related cancers, there has been an amplification of the receptor protein rather than a mutation of the gene (Kobus and Fleming (2005) Biochemistry 44:1464-70).
Protein tyrosine kinase 7 (PTK7), a member of the receptor protein tyrosine kinase family, was first isolated from normal human melanocytes and cloned by RT-PCR (Lee et al., (1993) Oncogene 8:3403-10; Park et al., (1996) J. Biochem 119:235-9). Separately, the gene was cloned from human colon carcinoma-derived cell lines and named colon carcinoma kinase 4 (CCK4) (Mossie et al. (1995) Oncogene 11:2179-84). PTK7 belongs to a subset of RTKs that lack detectable catalytic tyrosine kinase activity but retain signal transduction activity and is thought to possibly function as a cell adhesion molecule.
The mRNA for PTK7 was found to be variably expressed in colon carcinoma derived cell lines but not found to be expressed in human adult colon tissues (Mossie et al., supra). PTK7 expression was also seen in some melanoma cell lines and melanoma biopsies (Easty, et al. (1997) Int. J. Cancer 71:1061-5). An alternative splice form was found to be expressed in hepatomas and colon cancer cells (Jung et al. (2002) Biochim Biophys Acta 1579: 153-63). In addition, PTK7 was found to be highly overexpressed in acute myeloid leukemia samples (Muller-Tidow et al., (2004) Clin. Cancer Res. 10:1241-9). By immunohistochemistry, tumor specific staining of PTK7 was observed in breast, colon, lung, pancreatic, kidney and bladder cancers, as described in PCT Publication WO 04/17992.
Accordingly, agents that recognize PTK7, and methods of using such agents, are desired.